Premium
Guinea pig hippocampal 5‐HT 1E receptors: a tool for selective drug development
Author(s) -
Klein Michael T.,
Teitler Milt
Publication year - 2009
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2009.05958.x
Subject(s) - ritanserin , 5 ht receptor , receptor , guinea pig , serotonin , radioligand , pharmacology , 5 ht2a receptor , hippocampal formation , biology , chemistry , endocrinology , biochemistry
Recent studies have indicated that the serotonin [5‐hydroxytryptamine (5‐HT)] 1E receptor, originally discovered in human brain tissue, is not expressed in rat or mouse brain. Thus, there have been few reports on 5‐HT 1E receptor drug development. However, expression of 5‐HT 1E receptor mRNA has been shown in guinea pig brain. To establish this species as an animal model for 5‐HT 1E drug development, we identified brain regions that exhibit 5‐carboxyamidotryptamine, ritanserin, and LY344864 – insensitive [ 3 H]5‐HT binding (characteristic of the 5‐HT 1E receptor). In hippocampal homogenates, where 5‐HT 1E receptor density was sufficiently high for radioligand binding analysis, 100 nM 5‐carboxyamidotryptamine, 30 nM ritanserin, and 100 nM LY344864 were used to mask [ 3 H]5‐HT binding at non‐5‐HT 1E receptors. The K d of [ 3 H]5‐HT was 5.7 ± 0.7 nM and is indistinguishable from the cloned receptor K d of 6.5 ± 0.6 nM. The affinities of 16 drugs for the cloned and hippocampal‐expressed guinea pig 5‐HT 1E receptors are essentially identical ( R 2 = 0.97). These findings indicate that using these conditions autoradiographical distribution and signal transduction studies of the 5‐HT 1E receptor in guinea pig brain are feasible. Using the guinea pig as an animal model should provide important insights into possible functions of this receptor and the therapeutic potential of selective human 5‐HT 1E drugs.